An update on antithrombotic therapy in atrial fibrillation: the role of newer and emergent drugs.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with potentially dreadful cardioembolic complications such as stroke. The risk of stroke is stratified based on the patient's comorbid conditions using several scoring systems. Patients are treated with oral anticoagulation using warfarin or aspirin based on their cardioembolic stroke risk. Although warfarin has been the only effective therapy, it is underutilized clinically due to concern for multiple drug-to-drug and drug-to-food interactions and hemorrhagic complications. Dual antiplatelet therapy with aspirin and clopidogrel has been studied as a potential alternative anticoagulant for AF patients; however, the combination of aspirin and clopidogrel was noted to be inferior to warfarin in preventing strokes, with an increased risk of bleeding. As a result, newer anticoagulant agents, including direct thrombin inhibitors, direct and indirect factor Xa inhibitors, and vitamin K antagonists, have been developed and evaluated in AF patients. Results from a recent study demonstrated that high-dose dabigatran, a direct thrombin inhibitor, was superior to warfarin in preventing stroke and systemic embolism with similar bleeding risk. It ultimately received approval by the US Food and Drug Administration for stroke prophylaxis for nonvalvular AF patients. There are several other direct factor Xa inhibitors currently under study. Dabigatran may be considered in AF patients who are intolerant to warfarin or unwilling or unable to follow-up with frequent laboratory monitoring. Other newer anticoagulant agents also provide us with possible suitable alternatives to warfarin, and their clinical use will depend on the results from ongoing studies.

An evidence-based review of apixaban and its potential in the prevention of stroke in patients with atrial fibrillation.

Atrial fibrillation (AF) is a common cardiac arrhythmia, especially in the elderly population. It is associated with cardioembolic complications, particularly strokes, resulting in severe functional deficit or death. AF patients are first stratified into low, intermediate, and high risk for thromboembolic events using the CHADS(2) and CHA(2)DS(2)-VASc score systems. Depending on their risks, patients are treated with either therapeutic anticoagulation with warfarin or acetylsalicylic acid for stroke prevention. Although warfarin is the recommended therapy, it is underutilized clinically due to concern for narrow therapeutic window, drug-to-drug and drug-to-food interactions, and hemorrhagic complications. Newer anticoagulant agents such as dabigatran (a direct thrombin inhibitor) and rivaroxaban (a direct factor Xa inhibitor) have already been approved by US Food and Drug Administration for stroke prevention in patients with nonvalvular atrial fibrillation. Apixaban is the newest oral direct factor Xa inhibitor and it has been extensively studied in the AVERROES and ARISTOTLE trials. Apixaban demonstrated reduced incidence of primary outcome of stroke and bleeding events when compared with warfarin. Apixaban is currently being reviewed by the Food and Drug Administration as a stroke prophylactic agent. In addition, there are several other indirect factor Xa inhibitors and vitamin K antagonists under study presently. Results from these studies will provide us with information about possible alternatives to warfarin.

Role of emerging antithrombotic therapy in the prevention of cardioembolic complications in patients with atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is an independent risk factor of potentially catastrophic cardioembolic strokes. AF patients are categorized into high-, intermediate-, and low-risk for thromboembolic complications using the CHADS(2) or CHA(2)DS(2)-VASc scoring system. Oral anticoagulation using warfarin has been the standard therapy for stroke prevention in intermediate- to high-risk AF patients. However, warfarin use has been limited by several factors such as narrow therapeutic windows, drug-drug and drug-food interactions, and hemorrhagic complications. Rigorous research evaluated dual antiplatelet therapy of clopidogrel and aspirin (acetylsalicylic acid) as a potential alternative to warfarin in the ACTIVE W trial. Dual antiplatelet therapy of clopidogrel and aspirin was found to be inferior to warfarin in preventing stroke and systemic embolism with increased bleeding risk. Other extensive research has led to the development of new antithrombotic agents. Recently, dabigatran etexilate 150 mg twice daily, a direct thrombin inhibitor, was approved by the US FDA for stroke prevention in patients with non-valvular AF after it was found to be superior to warfarin in preventing thromboembolic events and associated with less bleeding in the RE-LY trial. It was also cost effective when compared with warfarin. Dabigatran can be considered in high-risk AF patients who are unable or unwilling to comply with the frequent laboratory and clinic visits that are required when receiving treatment with warfarin. Factor Xa inhibitors are another class of new anticoagulants that have been developed. Oral rivaroxaban was non-inferior to warfarin in thromboprophylaxis and with similar bleeding in the ROCKET-AF trial (HR 0.88; p = 0.117). Apixaban, another factor Xa inhibitor, was superior to aspirin in reducing stroke and systemic embolism in patients with AF in the AVERROES trial (HR 0.45; p < 0.001). The results of the ARISTOTLE trial, which is evaluating apixaban against warfarin in ∼18 000 patients with AF, are expected to be available later this year. Edoxaban, another oral factor Xa inhibitor, is currently being evaluated against warfarin in the ENGAGE AF-TIMI 48 trial in ∼20 000 patients with AF. With these new developments, there is a necessity for the clinical practitioner to become familiar with these new and upcoming therapies and guidelines. This review provides an overview of the available data regarding the clinical usefulness of these agents.